The humoral mediators of acute inflammation can be divided into those that activate nociceptive afferents and produce pain (e.g., bradykinin), and those that sensitize, but do not activate nociceptors and produce hyperalgesia (e.g., E-type prostaglandins). However, the poor correlation between the concentration of inflammatory mediators and intensity of symptoms in certain pathological conditions (e.g., rheumatoid arthritis) and the failure of the aspirin-like drugs to consistently produce analgesia for the pain and hyperalgesia associated with inflammation suggest that other mediators are involved in producing these symptoms. We propose to study the contribution of leukotrienes, a newly discovered class of arachidonic acid metabolites, whose synthesis is not inhibited by aspirin-like drugs, to the pain and hyperalgesia associated with inflammation with a view toward improving symptom management in humans. In preliminary experiments we have already found evidence for a receptor-mediated hyperalgesic effect of leukotriene-B4.